The pharmacological management of asthma-chronic obstructive pulmonary disease overlap syndrome (ACOS)

ABSTRACT

Introduction: Asthma-chronic obstructive pulmonary disease overlap syndrome (ACOS) is a disease phenotype that shares T helper lymphocyte cell Th1/neutrophilic/non-Type-2 Inflammation pathways thought to be key in COPD and Th2/eosinophilic/Type-2 inflammatory pathways of asthma. The pharmacology of treating ACOS is challenging in severe circumstances.

Areas covered: This review evaluates the stepwise treatment of ACOS using pharmacological treatments used in both COPD and asthma. The most common medications involve the same inhalers used to treat COPD and asthma patients. Advanced stepwise therapies for ACOS patients are based on patient characteristics and biomarkers. Very few clinical trials exist that focus specifically on ACOS patients.

Expert opinion: After inhalers, advanced therapies including phosphodiesterase inhibitors, macrolides, N-acetylcysteine and statin therapy for those ACOS patients with a COPD appearance and exacerbations are available. In atopic ACOS patients with exacerbations, advanced asthma therapies (leukotriene receptor antagonists and synthesis blocking agents.) are used. ACOS patients with elevated blood eosinophil/IgE levels are considered for immunotherapy or therapeutic monoclonal antibodies blocking specific Th2/Type-2 interleukins or IgE. Symptom control, stabilization/improvement in pulmonary function and reduced exacerbations are the metrics of success. More pharmacological trials of ACOS patients are needed to better understand which patients benefit from specific treatments.

Abbreviations: 5-LOi: 5-lipoxygenase inhibitor; ACOS: asthma – COPD overlap syndrome; B₂AR: Beta₂ adrenergic receptors; cAMP: cyclic adenosine monophosphate; cGMP: cyclic guanosine monophosphate; CI: confidence interval; COPD: chronic obstructive pulmonary disease; CRS : chronic rhinosinusitis; cys-LT: cysteinyl leukotrienes; DPI: dry powder inhaler; EMA: European Medicines Agency; FDA: US Food and Drug Administration; FDC: fixed-dose combination; FeNO: exhaled nitric oxide; FEV₁: forced expiratory volume in one second; FVC: forced vital capacity; GM-CSF: granulocyte-macrophage colony-stimulating factor; ICS : inhaled corticosteroids; IL: interleukin; ILC2: Type 2 innate lymphoid cells; IP₃: Inositol triphosphate; IRR: incidence rate ratio; KOLD: Korean Obstructive Lung Disease; LABA: long-acting B₂ adrenergic receptor agonist; LAMA: long-acting muscarinic receptor antagonist; LRA: leukotriene receptor antagonist; LT: leukotrienes; MDI: metered-dose inhalers; M_N: M-subtype muscarinic receptors; MRA: muscarinic receptor antagonist; NAC: N-acetylcysteine; NEB: nebulization; OR: odds ratio; PDE: phosphodiesterase; PEFR: peak expiratory flow rate; PGD2: prostaglandin D2; PRN: as needed; RR: risk ratio; SABA: short-acting B₂ adrenergic receptor agonist; SAMA: short-acting muscarinic receptor antagonist; SDMI: spring-driven mist inhaler; Th1: T helper cell 1 lymphocyte; Th2: T helper cell 2 lymphocytes; TNF-α: tumor necrosis factor alpha; US : United States

KEYWORDS:

• COPD
• asthma
• ACOS
• Asthma Chronic Obstructive Pulmonary Disease Overlap Syndrome
• Treatment
• Bronchodilators
• immunotherapy

Article Highlight

• Asthma COPD overlap syndrome (ACOS) patients have clinical features of both asthma and COPD.

• Basic treatment strategies that focus on the use of inhalers used in the treatment of both asthma and COPD are foundational approaches for the treatment of ACOS patients.

• Inhaled short-acting beta₂-adrenergic agonists, short-acting muscarinic receptor antagonists, and combinations are used as relief medications in ACOS.

• Inhaled long-acting beta₂-adrenergic agonists, long-acting muscarinic receptor antagonists, and inhaled corticosteroids are basic maintenance therapies in ACOS patients.

• Advanced treatments for ACOS (Non-type 2 inflammatory pathway mediated) patients include treatments commonly used for COPD patients having frequent exacerbations.

• Advanced treatments for ACOS (Type 2 inflammatory pathway mediated) patients include treatments commonly used for atopic Type 2 inflammatory pathway asthma patients with frequent exacerbations.

• ACOS patients with Type 2 inflammatory pathway activation may respond to injectable biological disease modifiers used in atopic Type 2 inflammatory pathway asthma patients who have frequent exacerbations.

This box summarizes key points contained in the article.

Declaration of interest

The authors have no relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript. This includes employment, consultancies, honoraria, stock ownership or options, expert testimony, grants or patents received or pending, or royalties.

Reviewer disclosures

Peer reviewers on this manuscript have no relevant financial or other relationships to disclose.

Additional information

Funding

This manuscript has not been funded.